Glaucoma is characterized by elevated intraocular pressure (IOP) which may lead to blindness if not properly controlled by appropriate therapy. Three major drugs used medically to reduce IOP are epinephrine (an alpha and beta adrenergic agonist), timolol (a beta adrenergic antagonist), and pilocarpine (a cholinergic agonist). Although there has been widespread interest in the mechanisms by which these agents reduce IOP, previously it has not been possible to study hormone receptors or hormone effects directly on the isolated target cells which are likely to influence aqueous inflow and/or outflow. The prior studies of hormone receptors in cornea, iris and ciliary body tissues will provide useful information to begin the evaluation of individual target cells. Hopefully, by quantitatively measuring specific receptor characteristics, pharmacological dose-response relationships and agonist/antagonist relationships for those cells involved in the regulation of aqueous humor dynamics, we can gain a better understanding of the mechanisms by which adrenergic and cholinergic agents lower IOP. To achieve these goals, we have developed methods for isolating cells from the trabecular meshwork, ciliary body epithelium, and ciliary muscle and detecting hormone receptors in these cells. Other cell types, which may also be important in the action (or side effects) of adrenergic and cholinergic hormones will be considered during the course of the proposed studies. We will attempt to propagate the appropriate ocular cells in tissue culture where possible, since this might allow us to study human cells directly. Also, use of cultured cells may allow us to more fully investigate the cellular basis for hormone regulation of processes such as tachyphalaxis (e.g. down regulation of receptors or other mechanisms for reduced hormone responsiveness), differences between agonist and antagonist action, biochemical responses in the target cells, and potentially improved modulation of hormone effects. If information gained from these studies of cultured cells and target tissues can be correlated with studies of physiological and clinical effects of the hormones, it may be possible to develop improved approaches to the treatment of glaucoma.